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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun department of neurology and Neuroscience Center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment Center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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Passive activity enhances residual control ability in patients with complete spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2337-2347页

作者： Yanqing Xiao Mingming Gao Zejia He Jia Zheng Hongming Bai Jia-Sheng Rao Guiyun Song Wei Song Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina department of rehabilitation Evaluation China Rehabilitation Research CenterBeijingChina Cardiac Center Beijing Children’s HospitalCapital Medical UniversityBeijingChina The State Key Laboratory of Virtual Reality Technology and Systems Beihang UniversityBeijingChina department of rehabilitation Engineering China Rehabilitation Science InstituteBeijingChina

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury ***,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface *** this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord *** patients with chronic complete thoracic spinal cord injury were *** electromyography data from eight major leg muscles were acquired and compared before and after the passive activity *** results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of *** the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically *** findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.

关键词： complete spinal cord injury cycle training epidural electrical stimulation motor training passive activity physiological state spinal cord circuit surface electromyography volitional control task

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Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

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Neural Regeneration Research 2025年第1期20卷 130-138页

作者： Ilaria Martinelli Jessica Mandrioli Andrea Ghezzi Elisabetta Zucchi Giulia Gianferrari Cecilia Simonini Francesco Cavallieri Franco Valzania department of Neurosciences Azienda Ospedaliero Universitaria di ModenaModenaItaly Clinical and Experimental Medicine Ph.D.Program University of Modena and Reggio EmiliaModenaItaly department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly neurology Unit Neuromotor&Rehabilitation DepartmentAzienda USL-IRCCS di Reggio EmiliaReggio EmiliaItaly

Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal *** the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of *** superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized *** numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this *** this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during *** multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.

关键词： amyotrophic lateral sclerosis(ALS) autonomic extramotor genotype-phenotype multisystem involvement Parkinson’s disease sensory SOD1 superoxide dismutase 1 urinary vocal cord palsy

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Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

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Neural Regeneration Research 2025年第2期20卷 354-365页

作者： Li Xu Huiming Xu Changyong Tang department of neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor *** date,no effective treatment exists as the exact causative mechanism remains ***,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic *** most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets *** experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum *** this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model *** addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

关键词： aquaporin-4 experimental model neuromyelitis optica spectrum disorder pathogenesis

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NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou Ying Xiaoli Si Naijia Xue Yi Liu Ran Zheng Ying Chen Jiali Pu Baorong Zhang department of neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

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Role of resident memory T cells in neuroinflammatory and neurodegenerative diseases in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3227-3228页

作者： Kimitoshi Kimura department of neurology Kyoto University Graduate School of MedicineTokyoJapan department of Immunology National Center of Neurology and PsychiatryTokyoJapan

The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the development of various autoimmune diseases,such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Moreover,T cells are now recognized as a pivotal contributor to the pathology of neurodegenerative disorders,including Alzheimer's disease(AD),Parkinson's disease(PD),and multiple system atrophy.

关键词： diseases degenerative pathology

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Systematic Acupuncture Explains Acupuncture at Baihui(GV20) and Fengchi(GB20) Targeting the Inflammatory Response to Regulate Migraine

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Journal of Traditional Chinese Medicine 2025年

作者： MIN Yu ZHENG Meifeng SUN Ju PENG Zetong CAO Zhixian HUANG Xiaohua Medical College of Acu-Moxi and rehabilitation， Guangzhou University of Chinese Medicine department of rehabilitation Medicine， the Affiliated Panyu Central Hospital of Guangzhou Medical University

Objective: To take Baihui (GV20) and Fengchi (GB20) targeting inflammatory response to regulate migraine as an example to describe a new method for studying the mechanism of stimulating ***: The target information of Baihui (GV20) and Fengchi (GB20) was retrieved， and after intersection with migraine， Kyoto Encyclopedia of Genes and Genomes (KEGG)， Reactome， and UniProt Keywords were used for functional enrichment. After selecting the main pathway， rats were selected and nitroglycerin was used for modeling， and the behavioral scores， inflammatory factors， heme oxygenase 1 (HMOX1)， protein kinase B (AKT1)， signal transducer and activator of transcription 3 (STAT3)， phosphorylated extracellular signal-regulated kinase 1/2 (P-ERK1/ERK2) and other states of the rats in the acupuncture， twisting， and electroacupuncture groups were ***: A total of 135 Baihui (GV20) targets and 27 Fengchi (GB20) targets were collected. A total of 73 target information were obtained after the intersection of these targets in migraine. These 73 targets have three main pathways: hypoxia-inducible factor 1 (HIF-1) signaling pathway， signaling by interleukins and inflammatory response. The main targets in the pathway were verified and found that interleukin-1 beta (IL-1β)， interleukin-6 (IL-6)， tumor necrosis factor-alpha (TNF-α) and HMOX1， AKT1， STAT3， P-ERK1/ERK2 can be regulated by Baihui (GV20) and Fengchi (GB20).Conclusion: Baihui (GV20) and Fengchi (GB20) can regulate migraine by regulating inflammatory factors and HMOX1， AKT1， STAT3， P-ERK1/ERK2 and other changes in HIF-1 signaling pathway， Signaling by Interleukins and Inflammatory response pathways. Based on systems biology and network pharmacology， and with the model of "acupoint-target-disease"， explore the research methods of systematic acupuncture and moxibustion. We believe this is a usable research direction for exploring the mechanism of acupuncture stimulation.

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Cell polarization in ischemic stroke: molecular mechanisms and advances

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Neural Regeneration Research 2025年第3期20卷 632-645页

作者： Yuanwei Li Xiaoxiao Xu Xuan Wu Jiarui Li Shiling Chen Danyang Chen Gaigai Li Zhouping Tang department of neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

关键词： astrocyte polarization immune regulation inflammation ischemic injury microglia polarization neutrophil polarization signaling pathways stroke

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The dopaminergic system and Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2495-2512页

作者： Yuhan Zhang Yuan Liang Yixue Gu International Medical College Chongqing Medical UniversityChongqingChina College of Pharmacy Chongqing Medical UniversityChongqingChina department of neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqingChina

Alzheimer's disease is a common neurodegenerative disorder in older *** its prevalence,its pathogenesis remains unclea *** addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this *** is a crucial catecholaminergic neurotransmitter in the human ***-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical *** r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive *** review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related *** aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

关键词： adverse drug reaction Alzheimer's disease catecholamine dopamine receptor dopamine receptor heterodimers dopaminergic system neurodegenerative disease neurotransmitter signaling pathways traditional Chinese medicine treatment

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Genistein:a possible solution for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2903-2905页

作者： Karolina Pierzynowska Bartosz Karaszewski Grzegorz Węgrzyn department of Molecular Biology University of GdanskGdanskPoland Gdansk Polandand Department of Adult NeurologyFaculty of MedicineMedical University of GdanskGdanskPoland

Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous *** can lead to severe nervous system dysfunction,eventually affecting multiple organs and *** hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.

关键词： organs Alzheimer death

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